title: Adjuvant treatment with a mammalian target of rapamycin inhibitor, sirolimus, and steroids improves outcomes in patients with severe H1N1 pneumonia and acute respiratory failure.
abstract: OBJECTIVE
  Severe H1N1 pneumonia with acute respiratory failure results in infiltration of lungs due to the presence of hyperactive immune cells. Rapamycin and corticosteroids inhibit this immune response by blocking the activation of T and B cells.
  
  
  METHODS
  Open-label prospective randomized controlled trial.
  
  
  METHODS
  A tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan.
  
  
  METHODS
  Between 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients with severe H1N1 pneumonia and acute respiratory failure were enrolled.
  
  
  RESULTS
  Thirty-eight patients with confirmed H1N1 pneumonia and on mechanical ventilatory support were randomized to receive adjuvant treatment of corticosteroids with an mTOR inhibitor, either with sirolimus (Rapamune 2 mg/d) (sirolimus group, n = 19) for 14 days or without sirolimus (nonsirolimus group, n = 19). The clinical values measured included PaO2/FIO2, Sequential Organ Failure Assessment score, duration of ventilatory support, and mortality. The baseline demography was similar between the two groups. After treatment, the PaO2/FIO2 values on day 3 (167.5 [95% CI, 86.7-209.2 mm Hg], n = 19 vs 106.8 [95% CI, 73.0-140.7 mm Hg], n = 19; p = 0.025] and day 7 (241.6 [95% CI, 185.2-297.9 mm Hg], n = 19 vs 147.0 [95% CI, 100.7-193.7 mm Hg], n = 17; p = 0.008) in the sirolimus group were significantly better over the nonsirolimus group. Similarly, the Sequential Organ Failure Assessment score on day 3 (4.3 [95% CI, 3.1-5.5]; p = 0.029) and day 7 (5.9 [95% CI, 4.8-6.9], n = 19 and 6.2 [95% CI, 4.7-7.8], n = 17, respectively) significantly improved in the sirolimus group. The liberation from a mechanical ventilator at 3 months was also better in the sirolimus combined with corticosteroids treatment. Similarly, the duration of ventilator use was significantly shorter in the sirolimus group (median, 7 vs 15 d; p = 0.03 by log-rank test). In the sirolimus combined with corticosteroids treatment group, a rapid clearance of virus also occurred after 7 days of treatment.
  
  
  CONCLUSIONS
  In patients with severe H1N1 pneumonia, early adjuvant treatment with corticosteroids and an mTOR inhibitor was associated with improvement in outcomes, such as hypoxia, multiple organ dysfunction, virus clearance, and shortened liberation of ventilator and ventilator days.
authors.affiliation: 1Pulmonary Disease Research Center, Chang Gung Memorial Hospital, Linkou, Chang Gung University, College of Medicine, Taoyuan, Taiwan. 2Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University, College of Medicine, Taoyuan, Taiwan. 3Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 4Department of Thoracic Medicine, Chang Gung Memorial Hospital, Cha-Yi, Taiwan. 5Chang Gung Children's Hospital, Linkou, Taiwan.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Fu-Tsai
authors.initials: FT
authors.lastname: Chung
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Lin
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Huang
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chou
authors.forename: Kang-Yun
authors.initials: KY
authors.lastname: Lee
authors.forename: Tzou-Yien
authors.initials: TY
authors.lastname: Lin
authors.forename: Han-Pin
authors.initials: HP
authors.lastname: Kuo
mesh_terms: D000208:Acute Disease; D017024:Chemotherapy, Adjuvant; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011024:Pneumonia, Viral / Q000188:drug therapy*; D011239:Prednisolone / Q000627:therapeutic use*; D011446:Prospective Studies; D012131:Respiratory Insufficiency / Q000188:drug therapy*; D012720:Severity of Illness Index; D020123:Sirolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D011239:Prednisolone; D020123:Sirolimus